Multimodal Targeted Deep Sequencing of Circulating Tumor Cells and Matched Cell-Free DNA Provides a More Comprehensive Tool to Identify Therapeutic Targets in Metastatic Breast Cancer Patients

Cancers

Oliver Hoffmann¹  Sabine Kasimir-Bauer¹  Rainer Kimmig¹  Corinna Keup¹  Siegfried Hauch²  Markus Sprenger-Haussels²  Markus Storbeck²  Peter Hahn² 

[1] Department of Gynecology and Obstetrics, University Hospital of Essen, 45122 Essen, Germany;QIAGEN, 40724 Hilden, Germany;

关键词: liquid biopsy;    circulating tumor cells;    cell-free DNA;    circulating tumor DNA;    next-generation sequencing;    unique molecular indices;   

DOI  :  10.3390/cancers12051084

来源: DOAJ

【 摘 要 】

Cell-free DNA (cfDNA) and circulating tumor cells (CTCs) exhibit great potential for therapy management in oncology. We aimed to establish a multimodal liquid biopsy strategy that is usable with minimized blood volume to deconvolute the genomic complexity of metastatic breast cancer. CTCs were isolated from 10ml blood of 18 hormone receptor-positive and human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer patients. cfDNA was isolated from plasma generated after CTC depletion and targeted sequencing analyses were conducted. PIK3CA and ESR1 variants were less common in CTC gDNA, while ERBB2 variants were only detected in CTC gDNA. A total of 62% of all cfDNA variants were recovered in the matched CTC gDNA, while 72% of all variants were unique in either cfDNA (14 variants) or CTC gDNA (104 variants). The percentage of patients with no detectable cfDNA variants or CTC gDNA variants was 17%/11%, but a combined analysis identified variants in 94% of all patients. In univariate and multivariate regression models, ESR1 variants in cfDNA and CTC gDNA correlated significantly with survival. We suggest a coordinated analysis of both fractions in order to provide a comprehensive genomic footprint that may contribute to identifying the most suitable therapy for each individual.

【 授权许可】

Unknown